Phagocytic cells are geared primarily to the ingestion and killing of microorganisms. However, under certain conditions toxic agents are released from these cells with the potential for damaging adjacent tissues. The cytotoxic activity of human polymorphonuclear leukocytes and mononuclear phagocytes for tumor cells will be examined with particular emphasis on mediation of cytotoxicity by the myeloperoxidase-H2O2-halide and other oxygen-dependent systems including superoxide anion, hydroxyl radical and singlet oxygen. The studies proposed involve the use of cell-free model cytotoxicity systems as well as intact phagocytic cells. Mechanisms of action of cell mediated tumor cell cytotoxicity will be determined with the use of specific inhibitors and leukocytes from patients with defined abnormalities in leukocyte function. Potential means for imparting target cell specificity will be examined, including possible differences in susceptibility of malignant and non-malignant cells to damage, tumor cell directed chemotaxis of phagocytic cells and tumor specific antibody mediated phagocyte adherence and release of toxic agents. The proposed studies will define the function, mechanism of action and biological significance of human polymorphonuclear leukocytes and mononuclear phagocytes in defense of the host against neoplasia. BIBLIOGRAPHIC REFERENCES: Clark RA, Johnson FL, Klebanoff SJ, Thomas ED. Defective neutrophil chemotaxis in bone marrow transplant patients. J Clin Invest 58:22-31, 1976. Rosen H, Klebanoff SJ. Chemiluminescence and superoxide production by myeloperoxidase-deficient leukocytes. J Clin Invest 58:50-60, 1976.